Subcutaneous Bupivacaine Decrease Post-op Pain in Patients Undergoing C-Section

• Sponsor: Montefiore Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03383588
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 3
• Actual Duration (Months): 5.4
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if giving an injection of numbing medication at the incision at the end of cesarean will help control pain AFTER cesarean delivery. This study seeks to assess pain relief with incisional infiltration of local anesthetic during cesareans performed under spinal anesthesia also using intrathecal opioids. Participants will receive the usual regimen of pain medication in spinal anesthesia. At the end of the cesarean delivery, while the participants are still under the spinal medication, participants will receive an injection, at the incision, either numbing medication (with or without epinephrine) or sterile saline. After the cesarean delivery, participants will receive, by mouth, commonly prescribed pain medications - these medications are oxycodone (an opioid/ narcotic), acetaminophen (or more commonly known as Tylenol), and ibuprofen.

Condition or Disease	Intervention/Treatment	Phase
Pain, Referred	Drug: Bupivacaine; Drug: Morphine; Drug: Fentanyl; Drug: Epinephrine; Other: Saline solution	Phase 2

Detailed Description

The study assesses addition of subcutaneous bupivacaine with and without epinephrine to the standard intrathecal morphine/fentanyl combination given during spinal anesthesia during elective cesarean delivery on postoperative pain control as measured by postoperative usage of oral opioids and a postoperative pain assessment scale. Comparing post-op pain scores and oxycodone usage in patients who receive just intrathecal morphine to patients who receive intrathecal morphine plus subcutaneous bupivacaine .25%, to patients who receive bupivacaine .25% with epinephrine 1:200,000.

After cesarean delivery, all groups will actively control the use of post-operative pain medication by indicating to the care nurse whether or not pain medication is desired. Pain control for all groups will be the standard pain treatment: ibuprofen for mild to moderate pain and percocet (oxycodone) for severe pain.

The U.S. Food and Drug Administration (FDA) has approved bupivicaine as an anesthetic and for pain but the FDA has not approved bupivicaine to be given specifically for postoperative cesarean pain. Acetaminophen, oxycodone and ibuprofen are being used as part of routine clinical care for pain control after cesarean. Fentanyl and duramorph are being used in spinal anesthesia and are FDA approved for regional anesthesia and used for this purpose in routine clinical care.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Efficacy of Subcutaneous Infiltration With Local Anesthetic During Elective Cesarean Delivery for Postoperative Pain Control: a Randomized Controlled Trial
• Actual Study Start Date: Jul 19, 2018
• Actual Primary Completion Date: Aug 17, 2018
• Actual Study Completion Date: Dec 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: bupivacaine 0.25% standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25%	Drug: Bupivacaine; 20 ml subcutaneous bupivacaine (Marcaine) 0.25%. Bupivacaine is an anesthetic which can numb an area of the body to relieve pain during surgery or medical procedures, childbirth, and dental work.; Other Names: Marcaine ; Drug: Morphine; intrathecal morphine (Duramorph) 150mcg. DURAMORPH (morphine injection) is a systemic narcotic analgesic for administration by the intravenous, epidural or intrathecal routes. It is used for the management of pain not responsive to non-narcotic analgesics. DURAMORPH (morphine injection) administered epidurally or intrathecally, provides pain relief for extended periods without attendant loss of motor, sensory or sympathetic function.; Other Names: Duramorph ; Drug: Fentanyl; intrathecal fentanyl 10 mcg. Fentanyl (also spelled fentanil) is an opioid which is used as a pain medication and together with other medications for anesthesia.; Other Names: Opioid
Active Comparator: bupivacaine 0.25% + epinephrine standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25% with Epinephrine	Drug: Bupivacaine; 20 ml subcutaneous bupivacaine (Marcaine) 0.25%. Bupivacaine is an anesthetic which can numb an area of the body to relieve pain during surgery or medical procedures, childbirth, and dental work.; Other Names: Marcaine ; Drug: Morphine; intrathecal morphine (Duramorph) 150mcg. DURAMORPH (morphine injection) is a systemic narcotic analgesic for administration by the intravenous, epidural or intrathecal routes. It is used for the management of pain not responsive to non-narcotic analgesics. DURAMORPH (morphine injection) administered epidurally or intrathecally, provides pain relief for extended periods without attendant loss of motor, sensory or sympathetic function.; Other Names: Duramorph ; Drug: Fentanyl; intrathecal fentanyl 10 mcg. Fentanyl (also spelled fentanil) is an opioid which is used as a pain medication and together with other medications for anesthesia.; Other Names: Opioid ; Drug: Epinephrine; Epinephrine injection is used along with emergency medical treatment to treat life-threatening allergic reactions caused by insect bites or stings, foods, medications, latex, and other causes. Epinephrine is in a class of medications called alpha- and beta-adrenergic agonists (sympathomimetic agents). It works by relaxing the muscles in the airways and tightening the blood vessels.; Other Names: Adrenaline
Placebo Comparator: Saline Solution standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous NACL 0.9% (placebo)	Drug: Bupivacaine; 20 ml subcutaneous bupivacaine (Marcaine) 0.25%. Bupivacaine is an anesthetic which can numb an area of the body to relieve pain during surgery or medical procedures, childbirth, and dental work.; Other Names: Marcaine ; Drug: Morphine; intrathecal morphine (Duramorph) 150mcg. DURAMORPH (morphine injection) is a systemic narcotic analgesic for administration by the intravenous, epidural or intrathecal routes. It is used for the management of pain not responsive to non-narcotic analgesics. DURAMORPH (morphine injection) administered epidurally or intrathecally, provides pain relief for extended periods without attendant loss of motor, sensory or sympathetic function.; Other Names: Duramorph ; Drug: Fentanyl; intrathecal fentanyl 10 mcg. Fentanyl (also spelled fentanil) is an opioid which is used as a pain medication and together with other medications for anesthesia.; Other Names: Opioid ; Other: Saline solution; 20 ml subcutaneous NACL 0.9% - saline solution is the placebo; Other Names: Sodium Chloride

Outcome Measures

Primary Outcome Measures

1. Amount of Supplemental Oxycodone Used [4-24 hours post operative]

   Cumulative opioid pain medication used in the first 24 hours postoperatively as recorded in the medical record

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

• elective cesarean delivery

• planned spinal anesthesia

Exclusion criteria:

• Non-English speaking

• Urgent or emergent cesarean delivery

• Active labor [defined as: >4cm cervical dilation or regular contractions noted on tocometer (>2 contractions in a 10 minute period for 30 consecutive minutes)]

• Chronic antepartum opioid use

• History of substance abuse (alcohol or drug)

• Current tobacco use

• Chronic steroid use

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Albert Einstein College of Medicine/ Montefiore Medical Center	Bronx	New York	United States	10461

Sponsors and Collaborators

• Montefiore Medical Center

Investigators

• Principal Investigator: Jeffrey Bernstein, MD, Montefiore Medical Center

Study Documents (Full-Text)

• Informed Consent Form - May 18, 2018
• Study Protocol and Statistical Analysis Plan - Jul 11, 2018

More Information

Publications

None provided.

• Responsible Party: Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT03383588
• Other Study ID Numbers: 2017-8094
• First Posted: Dec 26, 2017
• Last Update Posted: Jan 13, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Pain, Referred; Epinephrine; Fentanyl; Morphine; Bupivacaine

Study Results

Participant Flow

Arm/Group Title	Bupivacaine 0.25%	Bupivacaine 0.25% + Epinephrine	Saline Solution
Arm/Group Description	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25%	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25% with Epinephrine	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous NACL 0.9% (placebo)
Period Title: Overall Study
STARTED	8	9	9
COMPLETED	8	9	9
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Bupivacaine 0.25%	Bupivacaine 0.25% + Epinephrine	Saline Solution	Total
Arm/Group Description	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25%	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25% with Epinephrine	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous NACL 0.9% (placebo)	Total of all reporting groups
Overall Participants	8	9	9	26
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	29	34	29	31
Sex: Female, Male (Count of Participants)
Female	8 100%	9 100%	9 100%	26 100%
Male	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	1 12.5%	1 11.1%	1 11.1%	3 11.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 11.1%	3 33.3%	4 15.4%
White	1 12.5%	1 11.1%	0 0%	2 7.7%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	6 75%	6 66.7%	5 55.6%	17 65.4%
Region of Enrollment (Count of Participants)
United States	8 100%	9 100%	9 100%	26 100%
Estimated Blood Loss (EBL) (ml of blood) [Mean (Full Range) ]
Mean (Full Range) [ml of blood]	900	855	744	830

Outcome Measures

1. Primary Outcome

Title	Amount of Supplemental Oxycodone Used
Description	Cumulative opioid pain medication used in the first 24 hours postoperatively as recorded in the medical record
Time Frame	4-24 hours post operative

Outcome Measure Data

Analysis Population Description

all patients

Arm/Group Title	Bupivacaine 0.25%	Bupivacaine 0.25% + Epinephrine	Saline Solution
Arm/Group Description	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25%	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25% with Epinephrine	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous NACL 0.9% (placebo)
Measure Participants	8	9	9
Mean (Full Range) [mg of supplemental oxycodone]	19	25	23

Adverse Events

Time Frame	The participants were followed for a period of 6 months after initial date of recruitment for adverse events via medical record review
Adverse Event Reporting Description	Does not differ
Arm/Group Title	Bupivacaine 0.25%		Bupivacaine 0.25% + Epinephrine		Saline Solution
Arm/Group Description	standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25%		standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous bupivacaine (Marcaine) 0.25% with Epinephrine		standard intrathecal bupivacaine (Marcaine) 0.75% 1.5-1.7 ml, intrathecal morphine (Duramorph) 150mcg plus intrathecal fentanyl 10 mcg + 20 ml subcutaneous NACL 0.9% (placebo)
All Cause Mortality
	Bupivacaine 0.25%		Bupivacaine 0.25% + Epinephrine		Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)		0/9 (0%)
Serious Adverse Events
	Bupivacaine 0.25%		Bupivacaine 0.25% + Epinephrine		Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		2/9 (22.2%)		2/9 (22.2%)
Hepatobiliary disorders
Postpartum re-admission to hospital (not OBGYN related)	0/8 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Pregnancy, puerperium and perinatal conditions
Large intraoperative blood loss	0/8 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Large intraoperative blood loss	0/8 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Postpartum readmission to hospital (OBGYN related)	1/8 (12.5%)	1	0/9 (0%)	0	0/9 (0%)	0
Large intraoperative blood loss	0/8 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	Bupivacaine 0.25%		Bupivacaine 0.25% + Epinephrine		Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/9 (0%)		0/9 (0%)

Limitations/Caveats

Early termination leading to small numbers of subjects and Technical problems with measurement leading to unreliable or uninterpretable data; Study terminated early secondary to similar study published showing no difference in outcomes

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.